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一家儿童医院伏立康唑和泊沙康唑治疗药物监测实践的特征分析

Characterization of Therapeutic Drug Monitoring Practices of Voriconazole and Posaconazole at a Pediatric Hospital.

作者信息

Duehlmeyer Stephanie, Klockau Christopher, Yu Diana, Rouch Jamie

出版信息

J Pediatr Pharmacol Ther. 2021;26(1):26-32. doi: 10.5863/1551-6776-26.1.26. Epub 2021 Jan 4.

Abstract

OBJECTIVES

To characterize the voriconazole and posaconazole serum trough ordering practices in patients receiving prophylactic and treatment antifungal therapy.

METHODS

A retrospective chart review over a 6-year period of pediatric patients who received voriconazole and/or posaconazole for >24 hours.

RESULTS

A total of 113 patients were included in this study and of these patients, 105 received voriconazole and 16 received posaconazole during the study period. Additionally, 167 trough levels were assessed in this study. Only 50% and 54% of levels were considered within goal recommendations for voriconazole and posaconazole, respectively. The median dose required to achieve goal trough concentration was dependent on drug, indication, and dosage form. Lastly, the most common adverse drug reactions (ADRs) were hepatoxicity, QTc prolongation, and CNS changes, which were in concordance with ADRs documented in the clinical trials for voriconazole and posaconazole. Approximately 20% of patients receiving either voriconazole or posaconazole died during the study period and the median trough in both groups was subtherapeutic.

CONCLUSIONS

Increased monitoring of trough concentrations may be warranted to prevent death or breakthrough invasive fungal infections. Further studies are warranted for assessing the relationship between trough concentrations and treatment outcomes as well as relationship between dosing and achieving goal trough concentrations.

摘要

目的

描述接受预防性和治疗性抗真菌治疗的患者伏立康唑和泊沙康唑血清谷浓度监测的情况。

方法

对接受伏立康唑和/或泊沙康唑治疗超过24小时的儿科患者进行为期6年的回顾性病历审查。

结果

本研究共纳入113例患者,其中105例在研究期间接受伏立康唑治疗,16例接受泊沙康唑治疗。此外,本研究评估了167次谷浓度。伏立康唑和泊沙康唑分别只有50%和54%的谷浓度处于目标推荐范围内。达到目标谷浓度所需的中位剂量取决于药物、适应证和剂型。最后,最常见的药物不良反应是肝毒性、QTc延长和中枢神经系统改变,这与伏立康唑和泊沙康唑临床试验中记录的不良反应一致。在研究期间,接受伏立康唑或泊沙康唑治疗的患者中约20%死亡,两组的中位谷浓度均低于治疗水平。

结论

可能需要加强对谷浓度的监测,以预防死亡或突破性侵袭性真菌感染。有必要进一步研究评估谷浓度与治疗结果之间的关系以及给药与达到目标谷浓度之间的关系。

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